Evidence for immune activation against oxidized lipoproteins in inactive phases of juvenile chronic arthritis

Objective, Oxidative stress contributes to joint inflammation and damage in rheumatoid arthritis. In a mobile inflamed joint, exercise induced multipl e cycles of hypoxia-reperfusion injury may lead to the creation of a redox environment in which oxido-reductase systems, by NADPH mechanisms, produce highly reactive chemical species (i.e., oxygen free radicals). We investiga ted 2 endproducts of lipid peroxidation, malonildialdehyde (MDA) and diene conjugates (DC), and the formation of antibodies against oxidized low densi ty lipoproteins (Ab oxLDL) in juvenile chronic arthritis (JCA), and assesse d the role of oxidative phenomena in different phases and subsets of this d isease. Methods, To assess the role of oxidative stress in JCA, we measured the end products of lipid peroxidation. MDA and DC: by the increase of absorbance a t 586 nm and 234 nm, respectively, and the levels of Ab oxLDL by ELISA in t he sera of 58 patients with JCA and 21 healthy controls. Due to crossreacti vity between Ab oxLDL and anticardiolipin antibodies (aCL), the sera were a lso tested by a standard ELISA for IgG-aCL. The patients were divided into 3 subsets: 29 with pauciarticular (pauci), 15 with polyarticular (poly), an d 14 with systemic (sys) onset disease, and then were subdivided, according to different variables appropriate to each subset, reflecting active and i nactive disease, into 30 active (14 pauci, 8 poly, 8 sys) and 28 inactive(1 5 pauci, 7 poly, 6 sys). Results. Levels of Ab oxLDL were significantly increased in the whole group of patients (566.6 +/- 263.0 vs 206.6 +/- 136.3 mU/ml; p < 0.001) and in e ach of the type of onset (pauci 660.8 <plus/minus> 272.1, p < 0.001; poly 3 41.3 <plus/minus> 134.7, p < 0.01; sys 497.8 <plus/minus> 114.8, p < 0.001) compared to controls. Ab oxLDL were higher in the inactive than in the act ive group (743.5 <plus/minus> 231.9 and 404.4 +/- 169.9; p < 0.001). MDA an d DC levels were not increased significantly in patients' sera. No patient was positive for IgG-aCL. Conclusion. These findings suggest that MDA and DC cannot be considered maj or markers of oxidative stress in JCA and that the Ab oxLDL may represent a delayed sign of oxidative stress previously induced by the inflammatory pr ocess in patients with JCA.